Cytoskeletal elements (e.g. microtubules) carry out a wide range of functions in cells, even though their constituent proteins (e.g. tubulin) are structurally simple. It has long been known that eukaryotic cells have evolved means to fine-tune the polymerization dynamics, structure, and mechanical properties of their cytoskeleton through post-translational modifications (PTMs), which enable them to regulate their functions rapidly and reversibly. Bacteria also have cytoskeletal proteins, which are ancestral homologs of the better-studied eukaryotic ones. Bacteria also post-translationally modify their cytoskeleton, but the physiological functions of these PTMs are unclear.
The bacterial cytoskeletal protein FtsZ is an ancestral homolog of tubulin and essential for cell division in nearly all bacteria. During division, short filaments of FtsZ move circumferentially around the division ring by a unique type of polymerization dynamics called ‘treadmilling’, and the filaments subsequently bundle together into larger assemblies. Many bacteria phosphorylate FtsZ at specific sites using eukaryotic-like serine/threonine protein kinases (STPKs), but it is unclear how these modifications regulate the physical properties and physiological functions of FtsZ.
In this project, you will use cutting-edge microscopy to investigate how bacterial cells use PTMs to exert control over cell division by altering the physical properties of their cytoskeleton. Specifically, you will look at FtsZ in the bacterium Corynebacterium glutamicum—a non-pathogenic relative of Mycobacterium tuberculosis that is widely used in biotechnology—and examine the effects of PTMs on three interrelated phenomena: (i) FtsZ treadmilling dynamics, (ii) FtsZ filament structure, and (iii) cell division. You will make genetic mutants of this bacterium that perturb the STPK-FtsZ system, and then observe the effects using both fluorescence and electron microscopy. You will primarily use advanced fluorescence microscopy to image FtsZ dynamics inside live cells, including with a powerful new method where bacterial cells stand vertically inside bacteria-shaped holes. Additionally, you will examine the structures of FtsZ filaments by purifying the proteins involved and imaging them with electron microscopy.
During this project, you will be based in the Centre for Bacterial Cell Biology, a world-class research centre specialized in studying bacteria. In this collegiate environment, you will be surrounded by other students and staff who share an interest in understanding the biology of bacteria at a fundamental level. You will develop solid hands-on knowledge of molecular biology, biochemistry, and genetics techniques. Moreover, you will gain ample skills in both fluorescence and electron microscopy, including the increasingly valuable skills of image processing and analysis.
HOW TO APPLY
Applications should be made by emailing [Email Address Removed] with:
· a CV (including contact details of at least two academic (or other relevant) referees);
· a covering letter – clearly stating your first choice project, and optionally 2nd ranked project, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University;
· copies of your relevant undergraduate degree transcripts and certificates;
· a copy of your IELTS or TOEFL English language certificate (where required);
· a copy of your passport (photo page).
A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.
In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
Informal enquiries may be made to [Email Address Removed]
The deadline for all applications is 12noon on Monday 9th January 2023.
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